BACKGROUND INFORMATION: During embryonic development, beta-catenin is central both to the transcriptional activation of Wnt [wingless-type MMTV (murine-mammary-tumour virus) integration site family] target genes and as a mediator of cell-cell adhesion. Signals that regulate its levels and subcellular localization are critical. One mechanism of Wnt signalling results in stabilization of beta-catenin protein, which leads to its translocation into the nucleus, where it interacts with TCF (T-cell factor, HMG box) and activates transcription of target genes. Less well understood are mechanisms of Wnt signalling that do not involve beta-catenin stabilization and result in inhibition of beta-catenin-mediated transcription. RESULTS: Here, we show that a member of the Wnt protein family, Wnt4 (Wnt, member 4), regulates the subcellular localization of beta-catenin, redirecting it to the cell membrane. Unique among Wnts, this action does not affect the stability of beta-catenin but does prohibit its involvement in TCF gene transactivation. CONCLUSIONS: This novel mechanism suggests that Wnt4 acts as a switch between the two modes of beta-catenin function, transcriptional activation and cell-cell adhesion.
BACKGROUND INFORMATION: During embryonic development, beta-catenin is central both to the transcriptional activation of Wnt [wingless-type MMTV (murine-mammary-tumour virus) integration site family] target genes and as a mediator of cell-cell adhesion. Signals that regulate its levels and subcellular localization are critical. One mechanism of Wnt signalling results in stabilization of beta-catenin protein, which leads to its translocation into the nucleus, where it interacts with TCF (T-cell factor, HMG box) and activates transcription of target genes. Less well understood are mechanisms of Wnt signalling that do not involve beta-catenin stabilization and result in inhibition of beta-catenin-mediated transcription. RESULTS: Here, we show that a member of the Wnt protein family, Wnt4 (Wnt, member 4), regulates the subcellular localization of beta-catenin, redirecting it to the cell membrane. Unique among Wnts, this action does not affect the stability of beta-catenin but does prohibit its involvement in TCF gene transactivation. CONCLUSIONS: This novel mechanism suggests that Wnt4 acts as a switch between the two modes of beta-catenin function, transcriptional activation and cell-cell adhesion.
Authors: Yi Cai; Mark S Lechner; Deepak Nihalani; Marc J Prindle; Lawrence B Holzman; Gregory R Dressler Journal: J Biol Chem Date: 2001-11-07 Impact factor: 5.157
Authors: Haruhiko Akiyama; Jon P Lyons; Yuko Mori-Akiyama; Xiaohong Yang; Ren Zhang; Zhaoping Zhang; Jian Min Deng; Makoto M Taketo; Takashi Nakamura; Richard R Behringer; Pierre D McCrea; Benoit de Crombrugghe Journal: Genes Dev Date: 2004-05-01 Impact factor: 11.361
Authors: M Shtutman; J Zhurinsky; I Simcha; C Albanese; M D'Amico; R Pestell; A Ben-Ze'ev Journal: Proc Natl Acad Sci U S A Date: 1999-05-11 Impact factor: 11.205
Authors: Caroline M Alexander; Shruti Goel; Saja A Fakhraldeen; Soyoung Kim Journal: Cold Spring Harb Perspect Biol Date: 2012-10-01 Impact factor: 10.005